Modeling Biomarker-Guided Avoidance of Radical Cystectomy: Costs and Outcomes

Importance There is growing interest to avoid radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC) who receive neoadjuvant chemotherapy and achieve pathological complete response (ypCR). To achieve this goal, molecular biomarkers will likely need to be used to enhance clinical staging given the limitations of evaluation by cystoscopy, cytology, and cross-sectional imaging. There are no studies evaluating whether safe RC avoidance (SaRCA) would be cost effective and what impacts it would have on quality of life (QoL) and survival. Objective This study models the potential economic, QoL, and survival costs/benefits of a ypCR biomarker as it relates to SaRCA using a decision analysis and Markov Model (MM). Methods/Materials A decision tree and MM was created to compare the expected costs of initial treatment, QoL, and survival under one strategy where all patients undergo RC after neoadjuvant treatment versus an alternative strategy where all patients would be subjected to the biomarker test with biomarker-positive patients (those with presumed residual disease) undergoing RC, while biomarker-negative patients (presumed complete responders) would undergo surveillance for up to 20 years. ypCR rates to neoadjuvant therapy, survival with and without RC, quality adjusted life years (QALY), and costs were abstracted from the literature. Test cost, sensitivity, and specificity were also abstracted from the literature for multiple clinical or liquid biopsy approaches. Results Broadly, SaRCA approaches are cost effective with the exception of systematic endoscopic evaluation (SEE). All testing approaches result in higher QALY and overall life expectancy compared to no testing. The cost of the test is offset by decreased usage of RC to realize a cost savings. These domains are further improved when cisplatin-based chemotherapy is replaced with emerging neoadjuvant therapies. Conclusions and relevance Modeling supports the development of accurate biomarker tests which can distinguish residual disease states to enable SaRCA. Such a biomarker could be used to avoid an expensive and risky operation, and unexpectedly would provide a survival benefit by reducing the number of perioperative mortalities in patients achieving ypCR. Development of an accurate biomarker-based test is likely to reduce cost and increase QoL and survival. An accurate biomarker test would have utility for patients, payers, hospitals, and physicians.